IMBICE   05372
INSTITUTO MULTIDISCIPLINARIO DE BIOLOGIA CELULAR
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
EphA3 stimulates axonal growth of retinal ganglion cells
Autor/es:
ORTALLI, AL; CARRI, NÉSTOR G.; CAFFULLI, M.; RAPACIOLI M.; PASQUALE E.B.; SCICOLONE, G.
Lugar:
San Diego, USA
Reunión:
Congreso; SfN; 2007
Institución organizadora:
Society for Neuroscience
Resumen:
The retinotectal system is useful to study topographic map formation because nasal retinal ganglion cells (RGC) connect to the caudal tectum and temporal ones connect to the rostral tectum in a spatially organized manner. Eph receptor tyrosine kinases and their ligands, the ephrins, are expressed in complementary gradients in both the retina and the tectum and contribute to guide retinotectal projections to their targets. Ephrin-As located in the caudal tectum repel temporal axons by activating the axonal EphA3. However, there is controversial evidence about the signal that stimulates axon growth to the caudal tectum. We showed in vitro that substrate-bound EphA3 ectodomain promotes axon growth differentially in nasal and temporal RGC in a dose dependent manner and that retinal ephrin-As are candidate receptors for EphA3. The low level of expression of ephrin-As in temporal retina, however, makes it difficult to support this role in temporal RGC. Therefore, we investigated: 1) the expression pattern of ephrin-As in growth cones; 2) the stimulating properties of soluble EphA3; 3) the effects of the overexpressed-EphA3 ectodomain in the tectum on the location of the optic fibers. Retinal explants from 7 days-old chicken embryos were used for in vitro assays. We found that ephrin-A6 is highly expressed in nasal, moderately in dorsotemporal and very faintly in ventrotemporal growth cones. In agreement, aggregates of EphA3Fc differentially stimulate axon growth of nasal and dorsotemporal RGC whereas they do not stimulate axon growth of ventrotemporal RGC. Besides, all explants show a similar level of expression of EphA4, but in agreement with the level of expression of ephrin-As, the tyrosine-phosphorylation pattern shows less reactive axons in temporal explants. Retroviral vectors were used to overexpress the EphA3 ectodomain in the tectum and to label RGC axons with green fluorescent protein in the retina of 2-3 days-old embryos. At later stages of development we found that some nasal axons overpass the tectal surface without establishing termination zones.The results show that EphA3 stimulates axon growth in a substrate-bound and a soluble way in a concentration and aggregation dependent manner. This supports the idea that EphA3 acts in a gradient along the tectum. The fact that the response of growth cones is related to the level of expression of ephrin-A6 suggests that this molecule could act as a receptor for EphA3. The in vivo results suggest that EphA3 could be the stimulating force that guides axons towards the caudal tectum. Support: UBA Grant M096 CONICET PIP 6003 PIP 6176. Society for Neuroscience. 37th Annual Meeting. San Diego, USA. Aceptado.  (3-7/11/2007). 2007-A-113569-SfN Program#/Poster#: 460.1/E33 Location: San Diego Convention Center: Halls B-H Monday, Nov 05, 2007, 1:00 PM - 2:00 PM 2007 Copyright by the Society for Neuroscience all rights reserved.